The aim of this Mentored Research Scientist Development Award is to facilitate the candidate's development into a successful clinical neuroscience researcher investigating the neurodevelopmental basis of borderline personality disorder (BPD), particularly the role of adolescent maturation of cognitive and emotional control processes. Emotion dysregulation and impulsivity are prototypic features of BPD that typically emerge during adolescence and are associated with the persistence of BPD-related impairment over time. The immediate research priority of the proposed K01 award is to test the hypothesis that the development of these BPD symptoms in adolescence reflects dysfunctional adolescent maturation of connections among striatal, limbic, and prefrontal brain regions that support approach, avoidance, and modulatory neurobehavioral systems, respectively. The candidate has expertise in several domains relevant to studying the developmental psychopathology of BPD, including 1) the assessment of cognitive and emotion control processes using laboratory paradigms, 2) the behavioral and psychophysiological links between control processes and emotion dysregulation, and 3) the use of longitudinal data analytic methods to characterize developmental trajectories in BPD. To build upon this expertise and to focus specifically on the neural basis of BPD, the candidate will obtain further training in 1) developmental neuroscience approaches to the study of self-regulatory processes, 2) developmental psychopathology of BPD, and 3) functional and effective connectivity analyses to elucidate developmental changes in interregional connectivity during adolescence. Proposed research and training activities will be supported by the Laboratory of Neurocognitive Development directed by Dr. Beatriz Luna (primary mentor for this award), a noted developmental neuroscientist whose research has focused primarily on the protracted maturation of reward and control processes during adolescence. During the award, the candidate will conduct an fMRI study to characterize the maturation of interregional connectivity among the subgenual anterior cingulate cortex, ventral striatum, and amygdala during adolescence and early adulthood in healthy controls and individuals with BPD symptoms. Using functional and effective connectivity analyses, this study will characterize the balance of limbic-prefrontal and striatal- prefrontal influence during an emotion conflict task. The proposed research will also explore the prospective relationship between fronto-striatal-limbic connectivity and the developmental trajectory of BPD symptoms over an 18-month follow-up period. Consistent with the priorities of the National Institute of Mental Health, the proposed award has the potential to identify critical risk windows in the development of BPD using novel neurobiological methods. Further, the proposed award will provide the training and research experiences that will propel the candidate into a successful research career studying the neurodevelopment of BPD.

Public Health Relevance

Borderline Personality Disorder (BPD) is a complex psychiatric disorder associated with aggressive, suicidal, and self-injurious behaviors that often require intensive long-term treatment, resulting in significant treatment costs. Although this disorder is disproportionately represented in inpatient and outpatient mental health settings relative to its prevalence in the population, little is known about the factors that lead to the onet of BPD symptoms during adolescence. The proposed research seeks to identify how brain changes in adolescence are related to the development of BPD, which may inform prevention and treatment programs that result in improved outcomes for patients.